Back to Search
Start Over
Curvature-sensing peptide inhibits tumour-derived exosomes for enhanced cancer immunotherapy.
- Source :
-
Nature materials [Nat Mater] 2023 May; Vol. 22 (5), pp. 656-665. Date of Electronic Publication: 2023 Mar 23. - Publication Year :
- 2023
-
Abstract
- Tumour-derived exosomes (T-EXOs) impede immune checkpoint blockade therapies, motivating pharmacological efforts to inhibit them. Inspired by how antiviral curvature-sensing peptides disrupt membrane-enveloped virus particles in the exosome size range, we devised a broadly useful strategy that repurposes an engineered antiviral peptide to disrupt membrane-enveloped T-EXOs for synergistic cancer immunotherapy. The membrane-targeting peptide inhibits T-EXOs from various cancer types and exhibits pH-enhanced membrane disruption relevant to the tumour microenvironment. The combination of T-EXO-disrupting peptide and programmed cell death protein-1 antibody-based immune checkpoint blockade therapy improves treatment outcomes in tumour-bearing mice. Peptide-mediated disruption of T-EXOs not only reduces levels of circulating exosomal programmed death-ligand 1, but also restores CD8 <superscript>+</superscript> T cell effector function, prevents premetastatic niche formation and reshapes the tumour microenvironment in vivo. Our findings demonstrate that peptide-induced T-EXO depletion can enhance cancer immunotherapy and support the potential of peptide engineering for exosome-targeting applications.<br /> (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
Details
- Language :
- English
- ISSN :
- 1476-4660
- Volume :
- 22
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Nature materials
- Publication Type :
- Academic Journal
- Accession number :
- 36959501
- Full Text :
- https://doi.org/10.1038/s41563-023-01515-2